Genital Herpes Simplex

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Genital herpes simplex is caused by infection with the herpes simplex virus (HSV).

HSV is sub-divided into HSV type 1 (HSV-1) and HSV type 2 (HSV-2).

Type 1 is the usual cause of infections of the oral region and causes cold sores (herpes labialis). In the UK it is now also the most common cause of genital herpes.

Type 2 is associated with anogenital infection (penis, anus, vagina). It was the most common cause of genital infection but HSV-1 has overtaken it. HSV-2 is the most likely to cause recurrent anogenital infection.

However, both can infect the mouth and/or genitals, due to oral sex or auto-inoculation.

Epidemiology

This represented 7% of new diagnoses of a sexually transmitted infection (STI).

Rates have risen over the period of a decade.

Numbers of STIs in general have risen steeply in recent years for men who have sex with men. Genital herpes diagnosis rates rose by 10% in this population between 2013 and 2014.

42% of those diagnosed with genital herpes are 15-24 years of age.

Most people with genital herpes do not know they have the disease, so diagnostic rates significantly underestimate prevalence. Antibodies to HSV can be detected serologically and, as it is a lifelong disease, this may be used to determine prevalence more accurately. A number of studies worldwide have been done to estimate seroprevalence in specific populations. Results vary widely. There are no recent studies in the UK but an analysis published by the World Health Organization (WHO) in 2008 estimated global prevalence of HSV-2 (the most common cause globally) to be 16% of the worldwide population aged 15-49 in 2003.[3]Seroprevalence of HSV-1 is generally much higher.

Therefore, the infection is transmitted through vaginal, anal and oral sex, close genital contact and contact with other sites such as the eyes and fingers. Note:

The individual transmitting the infection may be asymptomatic but still shedding the virus. This is how most transmission of genital HSV occurs (at least 80% with proven HSV are unaware they have the infection).

Transmission from asymptomatic individuals in monogamous relationships can occur after several years and can cause considerable distress.

In many cases there are no symptoms and the infected person does not know they have the disease and does not present to the medical profession. Where the condition is symptomatic, it usually presents as multiple painful ulcers.

Primary infection

This is the first time the virus is acquired.

It may be asymptomatic (common).

A non-primary first episode refers to first presentation of symptoms in a person who has serological evidence of infection (shown by the presence of type-specific antibodies) with the other type of HSV in the past. Previous infection with one type of HSV modifies the clinical manifestations when the other is acquired.

Symptoms include:

Febrile flu-like prodrome (5-7 days). Myalgia and fever are the main systemic symptoms.

Tingling neuropathic pain in the genital area/buttocks/legs.

Extensive painful crops of blisters/ulcers in the genital area (including the vagina and cervix in women and the urethra in men).

Lesions are usually bilateral in primary disease (usually unilateral in recurrent cases).

Tender lymph nodes (inguinal). Usually bilateral in primary disease.

Local oedema.

Dysuria.

Vaginal or urethral discharge.

Systemic symptoms are more common in primary disease than in non-primary or recurrent disease.

It can last up to four weeks if not treated.

Recurrent infection

Following primary infection, the virus becomes latent in local sensory ganglia near to the skin.

There is periodic reactivation during which the virus moves from the ganglia to the skin. While the virus is in the skin, the patient may experience lesions (symptomatic shedding) or there may be no visible lesions (asymptomatic shedding). Reactivation experienced as symptomatic and asymptomatic shedding is always infectious.

Episodes are usually shorter (up to 10 days).

Symptoms may be mild and self-limiting.

Lesions tend to be unilateral.

Median recurrence rate after a symptomatic first episode is:

HSV-2: 0.34 recurrences per month (roughly four attacks in the subsequent 12 months).

HSV-1: 0.08 recurrences per month (roughly one attack in the subsequent 12 months).

Symptomatic and asymptomatic viral shedding become less frequent over time; however, it is possible to transmit the virus more than ten years after initial infection.[5]

It is important to confirm diagnosis and identify the type of HSV involved. This will affect management, prognosis and counselling.

Detection and identification of the virus

Suitable tests are:

Viral culture.

DNA detection using polymerase chain reaction (PCR) of a swab from the base of an ulcer. This increases rates of detection by up to 71% when compared with viral culture.

The choice of test depends on local availability, practicalities (eg, processing times and availability of appropriate refrigeration for specimens), cost and other factors. DNA detection by PCR is increasingly the more common method used.

Role of serology in HSV detection

Type-specific serology tests can identify those with asymptomatic infection and can distinguish between the two types of HSV.

Serological tests may take up to 12 weeks to become positive after primary infection.

It may be useful:

If a person's partner has genital herpes and the person wants to know if they have been infected.

If there are recurrent/atypical genital ulcers with negative culture or PCR results.

There is no cure for genital HSV. Infection is lifelong although most people will eventually stop having recurrences.

Referral

Ideally any person with suspected genital herpes should be referred to a genitourinary medicine (GUM) clinic. This allows accurate diagnosis, treatment, screening for other STIs, appropriate counselling, advice about recurrence, advice for partners and suitable follow-up.

If this is really not possible, confirm the diagnosis: swab the base of the ulcer or ulcer fluid for HSV (gently deroof the blister, if necessary using a sterile needle).[6]A special swab with transport medium is required - discuss this with your local laboratory. For culture specimens, maintenance of the cold chain and rapid transport of specimens within 24 hours is needed. PCR has a higher detection rate and does not require such careful handling of samples.

In the event that diagnosis and treatment have been based in primary care, arrange follow-up: arrange an appointment at a genitourinary medicine (GUM) clinic in 2 to 3 weeks to allow patient education and a full STI screen. Advise the patient to report to a GUM clinic sooner if the symptoms are not resolving. Provide the patient with written self-help information if possible.

Supportive management

Advice includes:

Saline bathing (one teaspoon of salt in one pint of warm water).

Oral painkillers.

Topical lidocaine 5% gel or ointment is suitable analgesia. Benzocaine, however, causes significant sensitisation and so is not recommended.[7]

Vaseline® or topical lidocaine may be applied to prevent pain during micturition.

Micturition whilst sitting in a bath can help prevent urinary retention.

Antiviral therapy

Topical antivirals have poor efficacy and have been found to cause aciclovir-resistant strains. They are, therefore, not recommended.[7]

Oral anti-herpes viral treatment should be given within five days of the onset of symptoms or if new lesions are still forming.

The British Association for Sexual Health and HIV (BASHH) guidelines advise first-line treatment should be five days of:

Aciclovir 400 mg three times daily; OR

Valaciclovir, 500 mg twice daily for five days.

BASHH alternative regimens (also for five days) are:

Aciclovir 200 mg five times daily; OR

Famciclovir250 mg three times daily.

Antiviral therapy reduces the severity and duration of episodes but does not alter the natural history of the disease

Management in people with HIV

This requires specialist advice. More detailed information is given in the BASHH guidelines.

Management in children

The presence of genital ulceration in a child may be alarming and has a broad differential diagnosis as listed above. According to the National Institute for Health and Care Excellence (NICE) guidelines, the presence of such lesions in a child should prompt the clinician to consider sexual abuse.[8]

This consideration involves:

Looking for other alerting features of abuse in the history and presentation.

Discussing the case with a more experienced clinician and/or a designated professional for safeguarding children.

Gathering collateral information from other health agencies and disciplines.

Ensuring review of the child.

The presence of genital ulceration in children should prompt a screen for other STIs. Examination of a prepubertal child should normally be undertaken by an experienced paediatrician, a suitably qualified forensic practitioner, or a GUM physician with appropriate expertise. A second adult/professional, who could attend primarily to the welfare of the child, should be present to provide explanation and support.[9]

Recurrence of infection usually causes less severe symptoms, which are more rapidly self-limiting.

Options for management are:

Supportive measures alone (as described above).

Antiviral therapy as required (episodic treatment).

Suppressive therapy.

Episodic antiviral treatment

Oral aciclovir, valaciclovir, and famciclovir have all been shown to reduce duration (by a median of 1-2 days) and severity of episodes of genital herpes. No advantage has been shown of one therapy over another. Short-course therapy has been found to be equally effective as five-day treatment. The earlier the treatment is started, the more effective it is likely to be. Therefore, people with recurrent genital herpes should have a course pre-prescribed so they can start it as soon as they feel the earliest symptoms developing.

BASHH advises the following short courses as options for first-line therapy:

Aciclovir 800 mg three times daily for two days.

Famciclovir 1 g twice daily for one day.

Valaciclovir 500 mg twice daily for three days.

Alternative five-day courses are:

Aciclovir 200 mg five times daily.

Aciclovir 400 mg three times daily.

Valaciclovir 500 mg twice daily.

Famciclovir 125 mg twice daily.

Suppressive antiviral treatment

May be needed (usually if >6 attacks per year).

Usual treatment is aciclovir at a dose of 400 mg twice daily or 200 mg four times daily.

Alternatives are famciclovir 250 mg twice daily or valaciclovir 500 mg once daily. A Cochrane review found no evidence to suggest efficacy of one treatment over another.[10]

Choice of treatment depends on cost, local guidelines and adherence.

Consider the frequency of attacks and symptoms vs the cost and inconvenience of treatment.

The suppressive effect takes five days of therapy to establish.

Discontinue after 12 months to reassess attack frequency. The minimum period of reassessment should include two further attacks. This is because discontinuing suppressive treatment commonly sets off a recurrence. If the recurrence rate is unacceptably high, suppressive treatment can be restarted.

Remember diagnosis can cause distress. Use appropriate language, avoiding terms such as "attack", "chronic", "incurable". Consider suggesting support from the Herpes Viruses Association, which has web-based information and a telephone helpline.[11]Written information should be given to the patient. Serological testing may be considered for asymptomatic contacts. Advise disclosure in all sexual relationships - this reduces the risk of transmission and may protect the person against legal action. Discussion about disclosure should be documented.

The following need to be covered:

Natural history of genital HSV. Explain it is possible to get genital herpes even if your partner has never shown any sign of infection. Explain the latent phase. Explain the role of asymptomatic viral shedding in sexual transmission (more common in genital HSV-2 and in the first year after infection). Stress the fact that a first episode of genital HSV does not necessarily imply recent infection. (Relationship issues need to be addressed.)

Informing of current or new sexual partners.

Use of antiviral drugs for symptom control, including prescription in reserve for recurrent attacks and possible longer-term suppressive treatment.

Reassurance that transmission cannot occur from sheets, towels, swimming pools, etc, including auto-inoculation after the initial infection has cleared.

Avoidance of sexual contact during symptomatic recurrences and prodromal phase.

Use of condoms. Condoms reduce (but do not completely prevent) the risk of transmission.

Pregnancy - the importance of not transmitting HSV to a pregnant woman should be stressed. Any woman with a diagnosis of genital herpes, or whose partner has genital herpes, should advise their GP and midwife of this at her first antenatal appointment, to consider how best to reduce the risk of neonatal infection. For more details see separate article Genital Herpes in Pregnancy.

Autonomic neuropathy, resulting in urinary retention. (Suprapubic catheterisation is preferred due to reduced risk of ascending infection, being a less painful procedure, and allowing normal micturition to be restored without multiple removals/recatheterisations.)

Perinatal transmission if the woman is pregnant - may cause serious complications in the neonate. See separate Genital Herpes in Pregnancy article.

Psychological and psychosexual problems.

In people with HIV with primary infection and no HIV therapy, there may be development of severe/prolonged mucocutaneous lesions. Other serious or life-threatening complications have been reported in this scenario - eg, fulminant hepatitis, pneumonia, neurological disease and disseminated infection.

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